Supervisore: Dr.ssa Maestro

A shRNA genetic screen to identify novel mediators of Epithelial to Mesenchymal Transition in cancer

Autophagy is a highly conserved catabolic process used by cells to renew cellular components. Addiction to autophagy in advanced tumors often associates with activation of epithelial to mesenchymal transition (EMT), a molecular program able to boost tumor cells aggressiveness.
Based on an in vitro shRNA genetic screen performed in triple negative breast cancer (TNBC) models, we identified as mediators of EMT a set of genes correlated with autophagy, among which ATG5.
Based on TCGA data we found that ATG5 expression correlates with poor prognosis in breast tumors, particularly in TNBC. Furthermore, exploiting an autophagy incompetent mutant (ATG5ϕdef) we collected evidence indicating that ATG5 induces EMT independently from autophagy.
The molecular mechanism by which ATG5 is engaged in EMT remains to be explained.
This project aims at dissecting molecularly the autophagy-independent functions of ATG5 in the development and progression of mesenchymal and mesenchymal like tumors.